According to the Alzheimer’s Association, TBI symptoms and related complications range in severity, depending on the extent of the damage to the brain. They may include loss of consciousness, memory loss, confusion, learning impairments, incoherent speech, lack of coordination and hearing or vision loss.

TBIs can have longer-lasting effects that do not appear until years later. The underlying reason for this is not well understood. Recent studies have found a link between TBI and risk for Alzheimer’s disease (AD). Research indicates that patients who have suffered a moderate to severe TBI are 2-4 times more likely to develop dementia than those with no history of TBI.

It is estimated that 5.5 million Americans of all ages - about 1 in 10 people over age 65 - were living with AD in 2017. With the anticipated growth of our aging population, the number of people with new and existing cases of AD is expected to increase to 13.8 million by 2050.

Projected number of people age 65+ in the US population with Alzheimer’s dementia (2010-2050)

Importantly, not every bump or blow to the head leads to AD. Experts agree that, in most cases, AD is probably the result of many factors, such as age, genetics, environment, lifestyle and other medical conditions. That said, many of the potential preventive measures have other positive health benefits. Those include wearing a seat belt in vehicles, fall-proofing your home, and wearing a helmet when playing sports or riding a bicycle or skateboard.

Inflammation: A Possible Link between TBI and AD

Cleveland Clinic Genomic Medicine Institute faculty member, Lynn Bekris, PhD, was recently awarded a $784,000 Department of Defense grant to compare the DNA (epigenetic) profiles of professional fighters that experienced TBI with the DNA profiles of AD patients and healthy control subjects in hopes of more accurately identifying individuals at increased risk for developing AD.

Studying epigenetics should help researchers understand whether and how TBI causes changes that can lead to AD. Epigenetics is an emerging field of study that examines how external or environmental changes alter the process by which cells “read” DNA - turning gene expression on or off - rather than changes to the DNA itself.

Bekris’s three-year project aims to provide critical missing information about neuroinflammation and its role in TBI, a risk factor for AD. Inflammation has been implicated as an important player in both TBI and AD.

The team will identify post-TBI individuals from the cohort of fighters that have a similar genetic- and epigenetic-related inflammation signature as seen in AD patients. They will then extract and compare RNA and DNA from blood samples to determine if there are common genetic and epigenetic changes across both groups of patients that can be identified as biomarkers for AD risk.

Findings from this study will yield important clues about how environmental exposure to brain injury influences disease. Specifically, it may help researchers identify individuals exposed to TBI who are susceptible to AD. Ultimately, it may offer information about how to treat TBI-related inflammation to facilitate a quicker recovery time after TBI and prevent long-term effects, such as AD.

Cross-Country Collaboration

The cohort of active and retired fighters will be from the Professional Fighters Brain Health Study (PFBHS), a study of professional fighters (ie, boxers and mixed martial artists) currently underway at the Lou Ruvo Center for Brain Health in Cleveland and Las Vegas. PFBHS participants undergo an annual comprehensive assessment that evaluates “quantitative traits”, such as magnetic resonance imaging, neuropsychological assessment and neurological examination, as well as genetic and biomarker analyses.

The AD cohort, as well as the healthy, non-TBI cohort serving as controls, will be from the Cleveland Clinic Center for Brain Health Biobank, a large biorepository dedicated to neurodegenerative research.

Lynn Bekris, PhD, is a principal investigator in Cleveland Clinic’s Genomic Medicine Institute. Her research focuses on identifying and evaluating the functional impact of genetic and epigenetic markers of Alzheimer’s disease.